Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.6.1.1 (aspartate aminotransferase)
21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biological response modifier 7-thia-8-oxoguanosine was evaluated in mice against the hepatotropic Adames strain of Punta Toro virus. When administered intraperitoneally in divided doses, significant protection from death was conferred at doses of 50 and 100 mg/kg/day given 24 and 17 h pre-virus inoculation, 25-100 mg/kg/day administered 4 h pre- and 3 h post-virus challenge, and 12.5 to 100 mg/kg/day administered 24 and 31 h after virus inoculation. These doses preventing death reduced liver icterus scores, serum alanine aminotransferase and aspartate aminotransferase levels, and liver and serum virus titers relative to placebo controls. Full daily doses administered at 24 h were somewhat less protective to mice than divided daily doses starting at the same time. The initiation of treatment could be delayed as late as 36 h after virus inoculation, resulting in complete protection from mortality at 100 mg/kg/day. This prevention of death occurred despite the acute nature of the infection which resulted in deaths by 96 h in the placebo-treated controls. These results show that 7-thia-8-oxoguanosine has both prophylactic and therapeutic potential as an anti-Phlebovirus agent. Interferon induction appears to be the reason for antiviral activity in this model, since up to 10,000 units of interferon/ml were induced in mice 1 h after treatment with 100 mg 7-thia-8-oxoguanosine per kg, and antibody to interferon alpha/beta administered shortly after treatment with the nucleoside negated the antiviral effect.
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PMID:Prophylactic and therapeutic activities of 7-thia-8-oxoguanosine against Punta Toro virus infections in mice. 171 90

Eighteen patients with biopsy proven chronic hepatitis B and markers of ongoing viral replication were treated with interferon alpha-2b (Intron A) while 24 similar patients served as control group. Permanent termination of HBV replication and normalization of ALT and AST activity was seen in 7 (39%) treated patients and in only two (8%) controls (p less than 0.05). Adverse reactions were few and subsided with the termination of therapy. These results of interferon therapy in chronic hepatitis B seem encouraging.
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PMID:[Treatment of chronic hepatitis B with interferon alfa-2b (Intron A)]. 184 9

We treated 41 chronic hepatitis C patients with recombinant interferon alpha 2a, 6 X 10(6) IU/day, for three weeks daily followed by intermittent therapy, 3 X 10(6) IU/day, three times weekly for 6 months and more. After 6 months of intermittent therapy, serum aminotransferases (AST, ALT) decreased to normal or nearly normal levels in 29 of 41 patients (70.7%) with histological improvement. The HCV (C100-3) antibody disappeared during and after IFN therapy in 7 of 34 HCV antibody positive patients (20.6%). Serum aminotransferases levels of all such patients were normalized or nearly normalized. The IFN antibody was detected in 8 of 41 patients (19.5%) including one whose IFN antibody was already present before starting IFN therapy. IFN treatment was discontinued in 22 of 41 patients (53.7%) because they responded completely or nearly completely to IFN therapy. All of the 22 patients have been maintaining normal aminotransferase levels for 1 to 24 months (mean, 12 months) after the treatment period. We conclude that long-term IFN therapy is greatly beneficial in controlling hepatic inflammatory changes in chronic hepatitis C.
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PMID:[Clinical study on long-term treatment of chronic hepatitis C with interferon]. 190 7

We have treated 17 patients with non-A, non-B chronic hepatitis by recombinant interferon alpha (0.3-9 megaunits for 4-28 weeks). In six patients, serum aminotransferase levels fell to normal or near-normal range during treatment. The mean levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in 17 patients fell from 156 +/- 80 (mean +/- SD) and 213 +/- 135 at the beginning of treatment to 94 +/- 49 and 112 +/- 71, respectively, at the end of treatment. In 12 patients, liver biopsies were performed before and after (or during) the treatment, and histological activity indices (HAI) were blindly examined by two independent observers. For comparison, we examined histological changes of pre- and posttreatment liver biopsies of 19 patients who were treated by recombinant interferon for chronic hepatitis B. Mean HAI scores improved from 10.0 to 5.4 after treatment in non-A, non-B chronic hepatitis. The most marked reduction was noted in scores of portal inflammation and hepatocellular degeneration and/or necrosis. No such reduction was observed in B-viral chronic hepatitis. These data indicated that rapid biochemical resolution by the treatment was related to histological improvement of the liver in our patients with non-A, non-B hepatitis.
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PMID:Histological changes of the liver by treatment of chronic non-A, non-B hepatitis with recombinant leukocyte interferon alpha. Comparison with histological changes in chronic hepatitis B. 249 64

Soluble intercellular adhesion molecule-1 (sICAM-1) is probably released from a variety of cells, including leukocytes and endothelial cells at sites of inflammation or in the circulation, and serum levels may therefore be used to give an indication of immune activation and inflammatory processes. In the present study, an ELISA was used to measure serum ICAM-1 levels in 43 patients with chronic hepatitis C and these were correlated with histological changes in the liver and the response to interferon alpha treatment. Serum ICAM-1 levels were significantly higher in patients with chronic hepatitis C infection than in normal subjects and correlated positively with the grade of histological activity, in particular the degree of portal, periportal, and lobular inflammation, but not with the presence of lymphoid aggregates. There was also a weak but significant positive correlation between sICAM-1 and serum aspartate aminotransferase activities, and sICAM-1 levels were substantially greater in patients with than those without cirrhosis. Serum ICAM-1 levels fell significantly in 11 responders out of 19 patients treated with interferon alpha, whereas levels remained unchanged in the non-responder group. sICAM-1 levels correlate with the clinical status of patients with chronic hepatitis C infection and fall with successful interferon treatment.
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PMID:Serum intercellular adhesion molecule-1 levels in chronic hepatitis C: association with disease activity and response to interferon alpha. 773 71

The intercellular adhesion molecule 1 (ICAM-1, CD54) and the lymphocyte associated antigen 3 (LFA-3, CD58) have been found in soluble form (sCD54 and sCD58) in human sera. Data concerning their role in chronic liver disease and their usefulness in disease monitoring are contradictory. We addressed the question whether elevated sCD54/sCD58 correlated either with disease activity or with decreased elimination secondary to reduced liver function in chronic hepatitis B. We studied 31 patients with chronic hepatitis B undergoing interferon alpha therapy in a longitudinal fashion. Serum concentrations of sCD54 and sCD58 were measured at four weeks interval by specific Sandwich ELISA during a follow-up period of ten months. The maximal difference in concentration of each biochemical parameter, e.g., delta AST, delta gGt, delta bilirubin, was determined for each patient during the whole follow-up period. These differences were correlated with the variation in sCD54 (delta sCD54) and sCD58 (delta sCD58) at the respective time points. Using this method, we were able to eliminate interindividual differences in serum concentrations for sCD54 and sCD58 and to avoid bias due to preselection of patients. We found that delta sCD54 correlated with delta AST (p = 0.001) and delta ALT (p = 0.002), whereas there was no such correlation for delta sCD58. Interferon therapy did not affect sCD54 or sCD58 levels. Neither hepatitis B viremia nor the immune response to hepatitis B during the time of seroconversion to anti-HBe did significantly increase sCD54 or sCD58 levels. However, delta sCD54 was associated with delta gamma GT (p = 0.005) and delta sCD58 correlated with delta bilirubin (p = 0.037); a negative correlation was found for delta sCD54 with delta cholinesterase (p = 0.007). Our findings imply that sCD54 and sCD58 may be associated with a decrease in liver function that accompanies hepatic disease activity. sCD54 and sCD58 did not prove useful to monitor disease activity or response to interferon therapy in chronic hepatitis B. From our data we conclude, that decreased elimination of soluble adhesion molecules sCD54 and sCD58 in advanced liver disease may be responsible for increased serum concentrations detected.
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PMID:Circulating ICAM-1 (sCD54) and LFA-3 (sCD58) in chronic hepatitis B--a longitudinal study in patients treated with interferon-alpha. 923 90

Resistance formation is a major problem in antiviral treatment of hepatitis B recurrence after liver transplantation. One possible therapeutic approach is an antiviral combination therapy with synergistic drugs. Four patients who were transplanted for chronic hepatitis B were analyzed retrospectively. All patients had reinfection of the graft and breakthrough of hepatitis B virus (HBV) during consecutive famciclovir and lamivudine monotherapy. Subsequently a combination therapy of lamivudine and interferon alpha 2a (3 times 3 million units weekly) was initiated. Addition of interferon markedly reduced viral replication rate in all patients. Three patients became HBV-DNA negative despite lamivudine resistance, but only two had a sustained response. No patient seroconverted to anti-HBe or lost HBsAg, but all patients showed a normalization of alanine aminotransferase and aspartate aminotransferase levels. No severe complications, and especially no rejection episodes occurred. Therefore lamivudine combined with interferon might be used for the therapy of hepatitis B reinfection after liver transplantation.
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PMID:Additional interferon alpha for lamivudine resistant hepatitis B infection after liver transplantation: a preliminary report. 1083 94

We report the case of a 64-year old woman with hepatitis C virus infection, mixed cryoglobulinemia type II (IgG + IgM kappa) and cryoglobulinemic glomerulonephritis. The patient was treated with the standard dose of recombinant interferon alpha-2b (3 million units 3 times a week) for one year, resulting in complete clinical remission and undetectable levels of serum hepatitis C virus RNA. AST and ALT normalized and proteinuria decreased from 2.78 to 0.98 g/day. However, a relapse occurred when therapy was stopped. Additional therapy with interferon-alpha (5 million units 3 times a week for 9 months) resulted again in quick and prolonged remission. The clinical course of our patient showed sustained clinical and virologic response after high-dose interferon-alpha treatment confirming the usefulness of interferon alpha in treatment of patients with cryoglobulinemic glomerulonephritis. Our observation is in agreement with others, suggesting that recommended standard dosage and duration of initial treatment with interferon alpha should be re-evaluated. Although our patient had sustained virologic and clinical response after interferon alpha monotherapy, recent studies clearly support combination therapy of interferon alpha and ribavirin for treatment of chronic HCV infections.
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PMID:Complete remission of cryoglobulinemic glomerulonephritis (HCV-positive) after high dose interferon therapy. 1094 19

Polymyositis is a rare complication of interferon alpha treatment as a result of immune-modulating role of the drug itself. In this case, interferon alpha induced polymyositis and cardiomyopathy is diagnosed in a 33-yr-old male patient with history of chronic hepatitis B. To treat hepatitis B, interferon alpha was administered until the proximal muscle weakness developed. Thereafter, sixteen cycles of immunoglobulin treatment (400 mg/kg) along with corticosteroids were instituted and led to an improvement in subjective symptoms with decreases in level of CPK and LDH. However, dilated cardiomyopathy has not improved in spite of the cessation of interferon treatment. Unlike the persistently elevated serum HBV DNA level, the serum ALT and AST levels have gradually decreased. Our case shows that clinical symptoms of polymyositis improved with steroid and immunoglobulin treatment without deterioration of the hepatitis B. To our knowledge, this is the first case of polymyositis associated with dilated cardiomyopathy after the administration of interferon in a patient with hepatitis B.
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PMID:A case of polymyositis with dilated cardiomyopathy associated with interferon alpha treatment for hepatitis B. 1185 Jun 6

Patients who will receive chemotherapy require careful assessment of liver function prior to treatment to determine which drugs are not appropriate, and which drugs need dose modification. However, if the hepatic parenchymal abnormalities are caused by an underlying neoplasm and the neoplasm is sensitive to the drugs, it may not be necessary to reduce the dose. Clearly, this is an area where clinical judgment must be used to assess the risk/benefit ratio. Treatment of chronic hepatitis B virus (HBV) involves either the nucleoside analogue lamivudine or interferon alpha. The advantage of lamivudine includes limited adverse effects and the fact that histological improvement has been documented in the majority of patients. Primary prophylaxis with lamivudine may be a well tolerated and effective method to reduce the frequency of chemotherapy-induced HBV reactivation in chronic HbsAg carriers. HbsAg screening is necessary before beginning chemotherapy for non Hodgkin's lymphoma patients. However, the main problem with long-term lamivudine therapy is the emergence of genotypic resistance because of base pair substitution at specific sites within the YMDD locus of the DNA polymerase gene. Significant hepatic dysfunction is uncommon among hepatitis C virus (HCV) infected patients treated with chemotherapy for hematological malignancies. However, infection with elevated AST levels is a significant risk factor for veno-occlusive disease after hematopoietic stem cell transplantation. Clinical judgment and a high index of suspicion remain critical tools in preventing and treating hepatic manifestations of cancer chemotherapy.
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PMID:[Hepatotoxicity of chemotherapy]. 1285 43


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